Within the NTDU group, we have utilized a number of automated, medium throughput assays to screen small compound collections against rat mixed cortical cultures, human neural stem cells (NSC) and human NSC-derived neurons and astrocytes. Weve utilized live cell imaging based assays with rat hippocampal and human neurons, as well as developed fluorescence-based assays to probe high content imaging endpoints. These cell based screening assays have been transferred to 384 well plate formats in order to increase our throughput. These assays have been employed in multiple screens with multiple investigators. We have continued to generate new chemical tool compounds in our chemistry labs to facilitate screening and mechanistic studies in our research projects. We produce and purify a number of recombinant proteins, such as Cdk5 and the HIV Tat protein for our own studies and provide that Tat protein to extramural researchers around the world for their studies. With the Section of Infections of the Nervous System (SINS), we have continued to work on multiple research projects. We continue to characterize the neurotoxicity resulting from the expression of the HERV-K env protein in NSC and human neurons. We are setting up a screen of HERV-K env neurotoxicity in human neurons in order to identify compounds that block env toxicity. The HIV Tat antagonist program has incorporated direct label-free binding assays as well as Tat-dependent selective LTR activation assays that will facilitate screening of the 14,000 compound Maybridge HitCreator collection for new lead Tat inhibitors. The NTDU has continued a number of studies in collaboration with other intramural investigators. We continue to work with Dr. Harish Pant and his research team to characterize the neuroprotective actions of the Cdk5 modulator TFP-5. In another series of experiments, treatment of neural stem cells with TFP-5 or its analog TP5 had no significant effect on NSC proliferation and self-renewal, but accelerated neuronal differentiation with nanomolar potency. Likewise, we continue to work with the Sibley research group to characterize the dopamine D3 receptor agonists that they have identified, using our live cell imaging platforms for quantitative analysis. We have recently begun working with two clinical investigators, Drs. Paul Lee and Michael Ward in screening projects involving new iPSC lines and their derived neurons and astrocytes.